We are conducting a series of clinical investigations involving patients with systemic lupus erythematosus in which questions related to disease pathogenesis, epidemiology, therapy and co-morbidities are addressed. Therapeutic studies in progress include a long-term, randomized trial of corticosteroids and immunosuppressive drugs in patients with severe, proliferative lupus glomeruonephritis and phase I/II of the nucleoside analog 2-chlorodeoxyadenosine and DNASE similarly in patients with lupus nephritis. Studies are underway to assess risk factors associated with the development of osteoporosis and vascular thrombotic events. Collaborative studies with scientists interested in lupus pathogenesis during the past year have included the influences of cytokines in autoimmunity (D. Klinman), antibody binding to chromatin adherent to the collagen of the glomerular basement membrane (J.B. Lefkowith), and FcgammaRIIa alleles as risk factors for nephritis in African-Americans (J.E. Salmon).